Molybedum-99 (Mo-99) production is one the largest and most complex radiopharmaceutical undertakings in the United States (U.S.). Northwest Medical Isotopes, LLC (NWMI) is designing, licensing, constructing, and will operate a radioisotope production capability that will support target fabrication, recovery and purification of the Mo-99 product from irradiated low-enriched uranium (LEU) targets, and uranium recovery and recycle to produce Mo-99. In addition, NWMI is continuing to complete research and development (R&D) on the radioisotope production facility (RPF) technologies and will compete development and licensing of the required irradiation and transport systems necessary to support RPF operations. The challenges of the project go beyond size and complexity. The challenges to produce a reliable and sustainable Mo-99 capacity include maintaining a long-term commitment to selected technologies, and the logical, step-by-step demonstration and safe application of those technologies to produce Mo-99 in the NWMI RPF on a weekly basis.